9-93452022-G-A

Position:

• chr9-93452022-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_014612.5(FAM120A):​c.107G>A​(p.Arg36Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,407,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM120A NM_014612.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39

Genes affected

FAM120A (HGNC:13247): (family with sequence similarity 120 member A) Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FAM120AOS (HGNC:23389): (family with sequence similarity 120 member A opposite strand) Differences in the expression level of this gene are associated with the survival rate of those with glioma. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), FAM120A. . Gene score misZ 3.3485 (greater than the threshold 3.09). Trascript score misZ 5.0695 (greater than threshold 3.09). GenCC has associacion of gene with Tourette syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.21890742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM120A	NM_014612.5	c.107G>A	p.Arg36Gln	missense_variant	1/18	ENST00000277165.11	NP_055427.2
FAM120AOS	NM_198841.4	c.563+125C>T		intron_variant		ENST00000375412.11	NP_942138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM120A	ENST00000277165.11	c.107G>A	p.Arg36Gln	missense_variant	1/18	1	NM_014612.5	ENSP00000277165	P3
FAM120AOS	ENST00000375412.11	c.563+125C>T		intron_variant		1	NM_198841.4	ENSP00000364561	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1407874 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 695820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000276

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.107G>A (p.R36Q) alteration is located in exon 1 (coding exon 1) of the FAM120A gene. This alteration results from a G to A substitution at nucleotide position 107, causing the arginine (R) at amino acid position 36 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;N
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.12
Sift	Benign	0.31	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.35	B;P
Vest4		0.13
MutPred		0.39		Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);
MVP		0.35
MPC		3.6
ClinPred		0.81	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.22
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-96214304;